Diagnosis of Primary Hepatic Lymphoma in a 55-Year-Old Male Patient Presented With Pain in the Right Hypochondrium: A Very Rare Case

Primary hepatic lymphoma (PHL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL). A 55-year-old male patient presented to us with jaundice and right upper quadrant pain. Investigations showed elevated alkaline phosphatase, lactate dehydrogenase, total bilirubin, normal alanine transaminase, and negative viral profile. Sonographic and computed tomographic scans show hepatosplenomegaly with hypodense lesion in liver associated with lymph nodes enlargement in the region of porta hepatis celiac axis, mediastinal and axillary lymphadenopathy. On immunohistochemistry, cells were positive for cluster of differentiation (CD)-19, CD-20, CD-21, c-myelocytomatosis oncogene (c-MYC), B-cell lymphoma 2 (Bcl-2), multiple myeloma oncogene-1 (MUM-1), same as B cell markers so it is diagnosed as PHL. DLBCL especially PHL shall be considered among the differentials of space-occupying lesions of liver. Early diagnosis of primary hepatic lymphoma is not a difficult task if excisional lymph node biopsy is taken following detection on ultrasound or CT scan which will lead to improved treatment, improvement in survival, and cost-effectiveness with good prognostic outcomes.


Introduction
Primary hepatic lymphoma (PHL) is a hepatic presentation of diffuse large B-cell lymphoma (DLBCL). Among all non-Hodgkin's lymphoma (NHL) cases, the DLBCL comprises 30-40% of cases [1]. DLBCL is predominantly common in the sixth or seventh decade of life [2]. It presents itself in two forms -nodal DLBCL and extranodal DLBCL. The nodal DLBCL presents mainly in the lymph nodes (64.8%), Waldeyer's ring (19.7%), mediastinum (12.8%), and the spleen (2.7%). Extranodal DLBCL involves stomach (22.4%), intestines (16%), nose and sinuses (8.9%), testis (8.4%), skin (7.9%), thyroid (6.9%), and CNS (6.4%), etc. while DLBCL involving the liver is a very rare type comprising only 0.4% [3]. Because of the very nonspecific presentation of DLBCL involving the liver, its diagnosis becomes challenging clinically and the need for excisional biopsy of the liver and sub-hepatic lymph nodes is highly important in establishing a specific diagnosis. This case depicts this unique presentation involving the liver and emphasizes the role of clinical symptoms and histopathological features suggestive of hepatic DLBCL which will help in detecting the disease at earlier stages and improve the survival rate, cost-effective health care, and better long-term prognosis.

Case Presentation
This 55-year-old patient was presented on November 8, 2021, with swelling and non-colicky pain in the right hypochondrium. It was associated with intermittent low-grade fever, night sweats, and weight loss from the past four months. There was anorexia but no vomiting, loose stool, or pain aggravation on eating. The patient also reported generalized body weakness affecting his daily activities. His physical examination was remarkable for mild jaundice and pallor, mild-to-moderate tenderness in the right hypochondrium, hepatomegaly of 15.5 cm, and splenomegaly of 11 cm in its largest diameter. Investigations done are given below in Table 1.  A CT scan of abdomen and pelvis (with contrast) was done on March 9, 2022, as described in (Table 2). This revealed enlarged liver and multiple enlarged lymph nodes; however, normal spleen, pancreas, and biliary tract. CT chest and neck done on March 9, 2022, showed multiple enlarged axillary and mediastinal lymph nodes (Figures 1, 2).

Liver
Enlarged measuring 16 cm in size, a hypodense, well-defined lesion measuring 18x16 mm was seen in segment 8 of the right lobe of liver.

Lymph nodes
Multiple enlarged lymph nodes at the porta hepatis, celiac axis, peri-pancreatic, pre-and para-aortic, and pre-caval region were seen. Largest lymph node measuring 3.8x4.1 cm at porta hepatis is anteriorly compressing the second part of duodenum and posteriorly compressing and displacing IVC.

4.
Gallbladder and biliary tract Normal  CT scan chest and neck (metastatic workup) done on January 4, 2022, showed multiple enlarged axillary and mediastinal lymph nodes described in Table 3. Axillary lymphadenopathy and mediastinal lymphadenopathies are shown in Figures 3, 4.

Cervical lymph nodes
No cervical lymphadenopathy.

2.
Axillary lymph nodes Enlarged bilateral axillary nodes were seen, the largest measuring 11.1 mm was seen in the right axilla.

Mediastinal lymph nodes
Enlarged mediastinal nodes were seen, the largest measuring 19 mm was seen in the right para tracheal region.

Lungs
Atelectatic bands were seen in both lungs; however, no nodules or mass noted.

FIGURE 4: Mediastinal lymphadenopathy on chest CT scan (arrow).
Biopsy and histopathology reports are described in Table 4 and Figures 5-9 and have been labeled. Ultrasound-guided core biopsy of sub-hepatic lymph node was done and histopathology showed diffuse infiltrate of intermediate to large-sized round to oval cells with scanty cytoplasm and darkly stained nuclei with open chromatin and occasional prominent nuclei consistent with diffuse large B-cell lymphoma. Immunohistochemistry slides have been shown in Figures 1-7.

Gross
Three tan-white colored cores and two core fragments measuring 0.5x0.2 cm.

Microscopic Diffuse infiltrates intermediate to large-sized round to oval cells with scant cytoplasm and darkly stained
nuclei with open chromatin and occasional prominent nuclei consistent with diffuse large B-cell lymphoma.

Treatment and follow-up visit
The patient is on rituximab with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-DA-EPOCH) therapy described in Table 5.
Immunohistochemistry of biopsied specimen can further aid in diagnosing PHL which will show cluster of differentiation (CD)-20 positivity, B-cell lymphoma 2 (Bcl-2), Bcl-6, multiple myeloma oncogene-1 (MUM-1), c-myelocytomatosis oncogene (c-MYC) positivity in 30-50% cases, sometimes CD-19 and CD-21 as well that is consistent with B-cell markers [9,10]. Treatment primarily consists of chemotherapy with R-CHOP regimen that includes rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovins, such as vincristine, prednisone, and sometimes etoposide [11]. Frequent follow-up visits for treatment response and management of chemotherapy-related side effects are crucial for improved health care outcomes including patient satisfaction and prevention of complications.

Conclusions
One of the differentials for the space-occupying lesions in the liver is primary hepatic lymphoma if other malignancies are ruled out. Early diagnosis of PHL is not a difficult task if lymph node excisional biopsy is taken following detection on ultrasound or CT scan which will lead to early treatment initiation, early disease remission with improved long-term survival, and cost-effective health care.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.